Sodium Channel Blockers
Severe
Textbook
May increase the risk of arrhythmia.
Avoid or use with extreme caution and monitoring.
Source: G&G 14e · p378
Drug reference
Lamotrigine
Phenyltriazine antiepileptic / mood stabilizer · Epilepsy
START
Verify no concurrent valproate (requires 50% dose reduction) or enzyme inducers (dose doubling needed). Baseline LFTs and CBC. Counsel on rash risk—stop immediately if rash appears.
TYPICAL MAX
Do not exceed 400mg/day monotherapy; with valproate max 200mg/day. Dose-related toxicity: diplopia, ataxia, tremor.
STOP IF
Any rash during first 8 weeks (SJS/TEN risk), fever with mucosal involvement, new suicidal ideation, hepatitis signs, aseptic meningitis symptoms.
WATCH
Drug interactions with valproate (↑levels), carbamazepine/phenytoin (↓levels), estrogen-containing contraceptives (↓levels by ~40-50%).
CDSCO approvedSchedule HATC N03AX09
KDIGO 2024 + manufacturer label
- ONSET
- 1h · Onset ~1 hour
- PEAK
- 2h · Tmax ~2 hours
- t½
- 1.2d · t½ ~25-33h (monotherapy)
- DURATION
- 1d · 24h (QD dosing)
EXCRETION
Renal as glucuronides (~70%)
route + CYP
INTERACTIONS
8 major
SEVERE in our sources
PREGNANCY
Risk of oral clefts (cleft lip/palate) in first trimester; folate supplementation (4-5mg) strongly recommended. Lamotrigine levels fall during pregnancy—monitor levels and adjust dose.
FDA category + note
Top interactionssee all 12 →
- Sodium Channel BlockersSevereTextbookG&G 14e · p378
- BuprenorphineSevereDatabaseDDInter
- DextropropoxypheneSevereDatabaseDDInter
- DivalproexSevereDatabase
Available in India
148 branded formulations. Look up specific brands in the Drugs workspace.
Mechanism
Blocks voltage-gated sodium channels and inhibits glutamate release; stabilizes presynaptic neuronal membranes and modulates calcium channels
Indications
Epilepsy (focal and generalized seizures)Lennox-Gastaut syndromeBipolar I disorder maintenance
Dosing
- Adult
- Epilepsy (monotherapy): 25mg daily x 2wk, then 50mg daily x 2wk, then 100mg daily, titrate to 200-400mg/day. Bipolar: 25mg daily x 2wk, then 50mg daily x 1wk, then 100mg daily, target 200mg/day (range 100-400mg).
- Pediatric
- Lennox-Gastaut: 0.3mg/kg/day x 2wk, then 0.6mg/kg/day x 2wk, titrate in 0.6mg/kg increments to 4.5-7.5mg/kg/day (with valproate: reduce by 50%).
- Renal adjustment
- Reduce dose by ~50% if CrCl <10 mL/min; titrate more slowly. Not removed by dialysis.
- Hepatic adjustment
- Reduce initial, escalation, and maintenance doses by ~25-50% in moderate impairment; use extreme caution in severe impairment.
- Geriatric
- Start at low end of dosing range; slower titration recommended.
- Max dose
- 400mg/day (adults, monotherapy); lower with valproate co-therapy
Pharmacokinetics
Onset
Variable; seizure control within 4-6 weeks of reaching therapeutic dose
Peak effect
Steady-state reached in ~5-6 half-lives (5-8 days monotherapy; 10-14 days with valproate)
Duration
24 hours with once-daily dosing at steady state
Half-life
25-33 hours (monotherapy); 48-59 hours with valproate; 13-14 hours with enzyme inducers
Bioavailability
~98%
Protein binding
~55%
Metabolism
Hepatic glucuronidation (primarily UGT1A4); no CYP involvement
Excretion
Primarily renal as glucuronide conjugates (~70%); ~10% unchanged in urine
Contraindications
- Hypersensitivity to lamotrigine
- Severe hepatic impairment
Side effects
Common
HeadacheDizzinessDiplopiaAtaxiaNauseaBlurred visionSomnolenceInsomnia
Serious
- Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Aseptic meningitis
- Blood dyscrasias
- Suicidal ideation
- Hepatic failure
Pregnancy & lactation
Pregnancy
Risk of oral clefts (cleft lip/palate) in first trimester; folate supplementation (4-5mg) strongly recommended. Lamotrigine levels fall during pregnancy—monitor levels and adjust dose.
Lactation
Excreted in breast milk (~30-50% of maternal plasma level); infant serum levels typically <30% of lower therapeutic range. Generally considered compatible with breastfeeding with monitoring.
Drug interactions
Buprenorphine
Severe
Database
Drug interaction classified as: synergy.
Source: DDInter
Dextropropoxyphene
Severe
Database
Clinical effect not specified
Source: DDInter
Divalproex
Severe
Database
Increased risk of severe lamotrigine-related rash (Stevens-Johnson syndrome, toxic epidermal necrolysis) and other CNS adverse effects (dizziness, ataxia).
Reduce lamotrigine starting dose and titration rate significantly when co-administered with divalproex. Monitor closely for rash and other adverse effects. Consider therapeutic drug monitoring for lamotrigine.
Dofetilide
Severe
Database
Clinical effect not specified
Source: DDInter
Sodium Oxybate
Severe
Database
.
Source: DDInter
Sodium Valproate
Severe
Database
Increased risk of severe rash (Stevens-Johnson syndrome, toxic epidermal necrolysis) and other lamotrigine-related adverse effects (e.g., dizziness, ataxia, nausea).
Initiate lamotrigine at a significantly lower dose (e.g., 25 mg every other day) and titrate very slowly. Monitor closely for rash and other adverse effects. Consider therapeutic drug monitoring for lamotrigine.
Valproate
Severe
Database
Valproate inhibits lamotrigine glucuronidation → toxicity/severe rash
Halve lamotrigine dose; very slow titration
Source: Kimi deep-research + Cla
Phenobarbitone
Moderate
Textbook
Lamotrigine's elimination half-life is reduced from 24 hr to approximately 16 hr.
Source: KDT 7e · p419
Carbamazepine
Moderate
Database
Enzyme-inducing AEDs increase lamotrigine glucuronidation, decreasing levels by ~40-50% and risking seizure breakthrough.
Double lamotrigine starting dose and titrate more rapidly; monitor seizure control.
Source: Kimi deep-research + Cla
Estradiol
Moderate
Database
Decreased plasma concentrations of lamotrigine, potentially leading to loss of seizure control. This effect is more pronounced with higher doses of estrogen.
Monitor lamotrigine levels and clinical response closely when initiating or discontinuing estradiol. Lamotrigine dose adjustment may be necessary. Consider alternative contraception if lamotrigine levels are difficult to manage.
Source: DDInter
Estrogen Containing Contraceptives
Moderate
Database
Estrogen induces UGT1A4, increasing lamotrigine clearance by 40-50%; levels drop and seizure risk increases.
Monitor lamotrigine levels during cycle; may need dose increase during active pills and reduction during pill-free week.
Source: Kimi deep-research + Cla
Related guidelines
Initial monotherapy for newly diagnosed epilepsy
ILAE · Neurology · 2013
Functional (psychogenic non-epileptic) seizures
AAN · Neurology · 2026
Initial monotherapy for newly diagnosed epilepsy
IAN · Neurology · 2023
Empirical antimicrobial use in common syndromes
ICMR · Infectious Diseases · 2019
Irritable bowel syndrome
ISG · Gastroenterology · 2023
Ask House about Lamotrigine
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: KD Tripathi 7e, Goodman & Gilman 14e, BNF·Verified: 2026-05-19 · House clinical team·Cockpit curated: 2026-05-19